That
might seem an odd thing to be optimistic about. Many of my colleagues
in physics are inspired by the prospect of achieving a Theory of
Everything. Some even claim that they've already got it. (Acknowledging,
to be sure, that perhaps a few i's remain to be dotted or a few
t's to be crossed.) My advice, dear colleagues: Be careful what
you wish for. If you reflect for a moment on what the words actually
mean, a Theory of Everything may not appear so attractive. It would
imply that the world could no longer surprise us, and had no more
to teach us.

I don't
buy it. I'm optimistic that the world will continue to
surprise us in fascinating and fundamental ways.

Simply
writing down the laws or equations is a long way from being able
to anticipate their consequences. Few physicists—and no sober
ones—seriously expect future work in fundamental physics
to exhaust, for example, neuroscience.

A less
literal reading of "Theory of Everything" is closer to
what physicists who use it mean by it. It's supposed to be a theory,
not really of everything, but of "everything fundamental".
And here "fundamental" is also being used in an unusual,
technical sense. A more precise word here might be "basic" or "irreducible".
That is, the physicists' Theory of Everything is supposed to provide
all the laws that can't be derived logically, even in principle,
from other laws. The structure of DNA surely emerges—in principle—from
the equations of the standard model, and I strongly suspect that
the possibility of Mind does too. So those phenomena, while they
are vastly important and clearly fundamental in the usual sense,
aren't fundamental in the technical sense, and elucidating them
is not part of a Theory of Everything.

I think
we're about to enter a new Golden Age in fundamental physics. The
Large Hadron Collider (LHC), which should begin to operate at CERN,
near Geneva, starting in summer 2007, will probe the behavior of
matter at energies higher than ever accessed before. There is no
consensus about what we'll find there. I'm still fond of a calculation
that Savas Dimopoulos, Stuart Raby and I did in 1981. We found—speaking
roughly—that we could unify the description of fundamental
interactions (gauge unification) only within an expanded version
of relativity, which includes transformations of spin (supersymmetry).
To make that dual unification we had to bring in new particles,
which were too heavy to be observed at the time, but ought to be
coming into range at the LHC. If they do exist we'll have a new
world of phenomena to discover and explore. The astronomical riddle
of dark matter could well be found there. Several competing ideas
are in play, as well. The point is that whatever happens, experimenters
will be making fundamental discoveries that take us by surprise.
That would be impossible, if we had a Theory of Everything in the
sense just described—that is, of everything fundamental.

In recent
months a different, much weaker notion of what a "Theory of
Everything" might accomplish has gained ground, largely inspired
by developments in string theory. In this concept, the Theory provides
a unique set of equations, but those equations that have many solutions,
which are realized in different parts of the Universe. One speaks
instead of a multiverse, composed of many domains, each forming
a universe in itself, each with its own distinctive laws. Now even
the fundamental—i.e., basic, irreducible—laws are beyond
the power of the Theory to supply, since they vary from universe
to universe. At this point the contrast between the grandeur of
the words "Theory of Everything" and the meager information
delivered becomes grotesque.

The
glamour of the quest for a Theory of Everything, or a Final Theory,
harks back Einstein's long quest for his version, a Unified Field
Theory. Lest we forget, that quest was fruitless. During his great
creative period, Einstein produced marvelous theories of particular
things: Brownian motion, the photoelectric effect, the electrodynamics
of moving bodies, the equality of inertial and gravitational mass.
I take inspiration from the early Einstein, the creative opportunist
who consulted Nature, rather than the later "all-or-nothing" romantic
who tried (and failed) to dictate to Her. I'm optimistic that She'll
continue to surprise me, and my successors, for a long time.

DAVID
DEUTSCHQuantum
physicist, Oxford University; Author, The
Fabric of Reality

About
Whether Solutions in General Are Possible

They
always are. Why is that important? Firstly, because it is true.
There is no anthropocentric spite built into the laws of physics,
mandating that human improvement may proceed this far and no further.
Nor is the dark, neo-religious fantasy true that Nature abhors
human hubris, and always exacts a hidden price that outweighs any
apparent success, so that 'progress' always has to be in scare
quotes. And secondly, because how we explain failure, both prospectively
and retrospectively, is itself a major determinant of success.
If we are optimistic that failure to improve ourselves always means
failure to find the solution, then success is never due to divine
grace (nowadays known as 'natural resources') but always to human
effort and creativity, and failure is opportunity.

I am optimistic about science education! I knew I should have
had a
psychological check-up, be tested for delusional fantasies, my
PhD revoked
in a public ceremony with the breaking of my pencils. After all,
in 1983, we
were officially declared "A Nation at Risk".

Commissions
galore like the
1999 Glenn Commission was entitled "Before it is too Late";
Education
Commission of the States "No Time to Waste", The Hart-Rudman
Commission
which came close to recommending that the budgets of Education
and Defense
be swapped!

Eminent CEO's like Bill Gates (Microsoft), Craig
Barrett
(Intel), Louis Gerstner (IBM), Norman Augustine (Lockheed Martin)
i.e.
Corporations which depend on rationality for their profits, all
agree that
our system of 50 independent States, 15,000 school districts,
26,000 high
schools etc etc has failed catastrophically to educate our students
for life
and work in the 21st century. But the good news is that the portent
of our
failed educational system as it impacts our health care, our
economy, our
culture and our status in the globalized world is finally becoming
clear,
clear to parents, clear to economists, clear, gasp! even to members
of the
Congress!

Somehow, we have created a sputnik-like climate warning
of a
powerful enemy...not the Soviets but even more worthy of a war
we must
declare and win: The War on Ignorance.

Out of Sputnik came the
National
Defense Education Act of 1958, NASA and a renewed determination
to
modernize science education, but also the conjugate communication
skills,
foreign languages and a need for public science literacy.

Can
one imagine
parents who know the earth revolves around the sun?

And for all
of the Edge scientists, an audience who might read their
stuff? Now there is wild
optimism!!

JILL
NEIMARKScience
Journalist; Co-author, Why
Good Things Happen To Good People

The
Human Epigenome Project

There
are maps, and then there are maps. We're embarking on a kind
of mapmaking that will usher in new ways of understanding ourselves-a
map that can explain why identical twins are not truly identical,
so that one succumbs to schizophrenia while the other remains
cognitively intact; why what your mom ate can save or sabotage
your health (as well as that of your children and your children's
children); and how our genetic fates can be tuned by such simple
universals as love or vitamins.

It's
The Human Epigenome Project (HEP). It's the next step after
the Human Genome Project, which in itself was as audacious
as the Apollo space program or the Manhattan Project, mapping
25,000 genes and the 3 billion pairs of bases in our DNA. And
yet, what The Human Genome Project mapped is like land without
borders, roads without names, a map without movement. Genes
are silent unless activated. To have them is not necessarily
to be under their influence.

"Land
lies in water, it is shadowed green," begins Elizabeth
Bishop's classic early poem, "The Map." The double
helix lies in the epigenome like land lies in water. The epigenome
is a flute playing a tune that charms the snake-coiled snake
that is the code of life-and the snake spirals upward in response.
A long bundle of biochemical markers all along the genome,
the epigenome responds to environmental signals and then switches
genes off or on, upregulates or downregulates their activity.
And in that change lies a great part of our destiny.

In
2003, in a widely discussed experiment, scientist Randy Jirtle
of Duke University Medical Center in Durham, North Carolina,
showed that he could change the activity of a mouse's genes
by giving supplements to its mom prior to, or during, very
early pregnancy. A mouse with yellow fur, whose offspring would
normally also be yellow, will give birth to brown-furred babies
if fed a diet supplemented with vitamin B12, folic acid, betaine
and choline. Even the offspring of the mom's offspring will
be born with brown fur. The genes themselves have not changed
at all, but their expression has, and that lasts for at least
two generations. And a fungicide used on fruits led to sperm
abnormalities in rats-abnormalities passed down at least four
generations. This gives us insight into nature's ways: apparently
she figures any change in the food supply will last a while,
and isn't just a seasonal fling.

Then,
in 2004, Moshe Szyf, Michael Meaney and their colleagues at
McGill University in Montreal, Canada, showed that love can
work in a similar way. If mothers don't lick, groom and nurse
their babies enough, a molecular tag known as a methyl group-a
tiny molecule made of three hydrogen atoms bound to a single
carbon atom-is added to a gene that helps regulate an animal's
response to stress. In pups that aren't nurtured properly,
the methyl group downregulates the genes' activity for life.
The pups have higher levels of stress hormones and are more
afraid to explore new environments. What is nature saying?
If a mom didn't attend to her newborn much, it's probably because
the environment was hostile and stressful. Better to be vigilant
and cautious, even afraid. Later, Meany and his colleagues
showed that a common food supplement could do exactly the same
thing to the genes of well-licked and nurtured rats. Once the
pups were three months old, researchers injected a common amino
acid, L-methionine, into their brains. This methylated the
same gene, downregulated it, and turned the rats into anxious
wallflowers.

Last
June, the European Human Epigenome Project published its first
findings on the methylation profiles, or epigenetics, of three
chromosomes. The push to map the epigenome is on. In the last
few weeks alone I've seen very different epigenetic stories
coming across the science wires. From the University of Texas
Medical Branch at Galveston came the news that breastfeeding
protects children who are genetically susceptible to repeated
ear infections because of common variants in their genes. The
tendency toward ear infections runs in families, and researchers
found the culprit in two gene variants that increase inflammatory
signaling molecules in the immune system. Remarkably, breast
milk seemed to permanently quiet the genes, so that even later
in childhood, long after the children had stopped breastfeeding,
they were protected from recurrent infections.

In
research from the Universidad Nacional Autonoma de Mexico and
the Instituto Nacional de Cancerologia, Mexico, epigenetic
drugs are now being studied in breast, ovarian and cervical
cancer. These drugs affect genes that, when reactivated, help
regulate cell proliferation, cell death, cell differentiation,
and drug resistance. They're cheaper than designer-name cancer
drugs, and might help increase survival rates.

Even
water fleas are joining the epigenetic act. In a December study
from the University of California at Berkeley expression of
genes in water fleas changed in response to common contaminants.
Water fleas are regularly used to monitor freshwater toxicity,
usually with a "kill 'em and count 'em" approach.
Researchers found that copper, cadmium and zinc decreased expression
of genes involved in digestion and infection. Screening like
this might help industry assess and avoid particularly toxic
contaminants.

Epigenetics
offers us a different kind of map. One where we can zoom in
and zoom out. A map of many colors, with street signs so we
can navigate, routes that we can choose, destinations that
we can change. Maybe the gene isn't selfish. Maybe it's actually
sensitive. "More delicate than the historian's are the
mapmaker's colors." So concludes Elizabeth Bishop's poem,
and the epigenome may prove to be one of the more beautiful,
delicate, subtle maps of all time.

I
am optimistic that open networks will continue to grow and become
available to more and more people. I am optimistic that computers
will continue to become cheaper and more available. I am optimistic
that the hardware and software will become more open, transparent
and free. I am optimistic that the ability to for people to create,
share and remix their works will provide a voice to the vast
majority of people.

I
believe that the Internet, open source and a global culture of
discourse and sharing will become the pillar of democracy for
the 21st Century. Whereas those in power as well as terrorists
who are not have used broadcast technology and the mass media
of the 20th century against the free world, I am optimistic that
Internet will enable the collective voice of the people and that
voice will be a voice of reason and good will.

Some
historians think the idea of democracy arose in the Greek soldier-sailors
of the 7th to 4th centuries BC who manned the trireme warships.
Up to sixty men—a deme—rowed these daunting three-tiered
ships. Their effectiveness in battle depended upon precise and
coordinated teamwork; the phrase 'pulling together' may have
its origin in the triremes. Deme-ocracy arose when the rower-fighters
realized that the same kind of coordinated pulling together that
powered the boat could be used to influence which battles their
masters had them fight and the conditions of their service. Herodotus
records that up to forty triremes were used when Samos invaded
the Egyptians—a lot of voting oarsmen. Modern democracies
owe a debt to the actions of these wretched fellows whose fates
were gambled by rulers who did not always have the rowers' best
interests at heart.

In
spite of this, and two and a half thousand years on, I am optimistic
that the world is glimpsing the limits of democracy. I speak
of democracy in its wider manifestations, and not just as government.
The common idea of democracy—that everyone has a 'right'
to be heard—naturally flourishes among the smallest collections
of people that can organise themselves into a group. To survive,
these groups compete for what they see as their share of the
pie. Look no further than the ultra-democracies of some Western
European nations, deadlocked coalition governments legitimized
from systems of proportional representation that reward small
special interest demes. Look to the intolerance that arises when
this or that group asserts rights over this or that groups' rights.
Look to 'focus groups'. Look to a state of numerical populism
in which the most votes or text messages or viewers is what is
to be delivered, crowned or sold. In the artist Paul Klee's words "democracy
with its semi-civilization sincerely cherishes junk". Strong
words perhaps, but there is that old saying about decision making
by committee.

The
British playwright Dennis Potter in a public speech not long
before his death defended the BBC—a decidedly undemocratic
and state-owned institution—for its very lack of populism.
To Potter the role of the BBC was to decide for the rest of us
the standards of what should be deemed good art, drama, history
and reporting, and to challenge us intellectually and aesthetically.
A dangerous state of affairs? Elitism? Maybe. But I am optimistic
that people are recognising that democracy simplistically applied,
without an eye on the larger Project, can easily descend into
an ochlocracy ruled by the groups that shout the loudest. Even
by the middle of the 19th century Disraeli was saying "the
world is wearied of statesmen whom democracy has degraded into
politicians".

A
hopeful sign: some nations and especially some American states
are researching new low carbon-footprint technologies and voluntarily
committing to what will be burdensome and expensive climate-change
targets. In most cases they are doing so without any democratic
mandate. They realize that there may be larger and longer term
stakes to play for than the 'right' to behave as one pleases
or to have what one wants. Maybe you know of other examples.

In
the coming year, we're going to witness a breakthrough in our
understanding of what sleep is for.

It
surprises most people to learn that this is even a question.
Every other basic bodily function—like eating, drinking,
breathing, urinating, or defecating—has a pretty clear
purpose. Our bodies and brains need food, water, and oxygen to
stay alive and to replenish themselves, and if they didn't rid
themselves of the byproducts of this metabolism, we'd be awash
in our own toxic waste. Likewise, sleep must be for something
important. We all spend decades in this strange state, immobilized,
unconscious, and vulnerable. But what exactly does sleep do for
us?

Parents
tell their children they need to sleep because they're tired
and need to rest. But of course rest is not good enough. Lying
still for eight hours is no substitute for sleep. My own mother
had a different theory. She said I needed to sleep because I
had too much "sleepy gas." It had been building up
all day long, and so I needed to sleep to get rid of it. In fact,
scientists observed a long time ago that if you keep a sheep
awake continuously for several days and then inject some of its
cerebrospinal fluid into another, well-rested sheep, that sheep
will fall right asleep, presumably because some naturally-occurring
sleep substance had reached a soporific level in the donor. But
this line of research never quite solved the puzzle. Although
a number of putative sleep substances have now been identified,
we're not sure how they might work biochemically, or how sleep
(as opposed to mere rest) might break them down.

Other
sleep-deprivation studies done in the early 1980's took a more
brutal approach, keeping rats awake for weeks until they died
from a lack of sleep, and then looking for the precise cause
of death. Such studies (now outlawed) could not pinpoint any
specific culprits, such as particular organ failures. One striking
observation, however, was that the rats ate much more than normal
and yet wasted away. Their metabolism seemed to be wrecked. So
maybe sleep is for energy regulation, in some unspecified way.
Other popular theories are that sleep is for tissue repair, or
immune function, or for consolidating learning and memory.

The
new development, and the cause for optimism, is an original approach
to the problem that makes the first quantitative, testable predictions
about the function of sleep. Two physicists, Van Savage (Harvard
Medical School) and Geoff West (Santa Fe Institute), have analyzed
how sleep varies across mammals of different species. Normally
physiological time ticks slower for bigger animals. For example,
elephants live much longer than mice and their hearts beat much
slower. The interesting thing is that both animals' lifetimes
and pulse times scale in the same way with their body mass—in
direct proportion to their mass raised to the 1/4 power—with
the curious implication that the hearts of mice and elephants
will typically beat the same number of times in their lifetime.

What
is so strange about sleep in this regard is that it behaves differently
from all other physiological times. It's backward. Mice sleep
longer than elephants, not shorter—about fourteen hours
a day compared to four. Savage and West interpret this as evidence
that sleep is related to cellular repair. They note that cells
produce destructive byproducts, such as free radicals, in the
course of normal metabolism, and they hypothesize that sleep
somehow helps repair the damage that ensues. (In this view, the
mouse needs to sleep longer to clean up all the byproducts generated
by its revved-up metabolism.). Then, using classic laws about
how metabolic rate varies across different species, they derive
mathematical predictions about how sleep duration should vary
with an animal's size. But which size is most relevant—brain
size or body size? The key is that they are not proportional.
If sleep is for repairing the brain, Savage and West derive one
prediction; if it's for repairing the body, they derive a different
prediction. When they finally confront their model with the available
data, they infer that sleep is mainly for repairing the brain,
not the body. So much for beauty sleep.

In
particular, I am optimistic about humanity's prospects for starting
exemplary new collaboratively-developed knowledge resources.
When we hit upon the correct models for collaborative knowledge-collection
online, there will be a jaw-dropping, unprecedented, paradigm-shifting
explosion in the availability of high-quality free knowledge.

Over
the last few years I have received an increasing amount of mail
from researchers who want to build dynamic, efficient, and enormous
new knowledge resources that follow the wiki model. I believe
researchers are drawn to the wiki model because they naturally
love several ideas suggested by the model: working closely with
large numbers of their colleagues spread over the world; updating
shared knowledge on the fly and avoiding costly duplication of
labor; presenting knowledge systematically and in all its glorious
complexity; and providing clear and compelling free access to
important knowledge of their fields to a world that, in many
cases, desperately needs such access. These features make the
wiki model exciting.

Researchers—scholars,
scientists, professionals of all sorts, and indeed, all folks
who love books—are, as I say, drawn to the wiki model of
strong collaboration in growing numbers. It's an accident of
history that methods of strong collaboration online began among
programmers and then spread into use by a completely egalitarian
community, Wikipedia, and its many imitators. The next step in
the evolution, which we are now witnessing on many fronts at
once, is the adoption of wikis, and similarly dynamic and efficient "Web
2.0" methods of strong collaboration, by knowledge workers,
or (as in the case of my new project, the Citizendium) huge open
communities that are gently guided by experts.

I
think the most fantastic knowledge resources of the near future
will not be encyclopedias or textbooks. They will be brand new
sorts of resources, never before possible because they require
the participation of thousands, or even millions, of users. What—for
example—can that quantity of people do with millions of
free books at their fingertips?

Assuming
as I do that expert-guided but public participatory free knowledge
projects are feasible, and that—after becoming convinced
of their tremendous value—millions of intellectuals from
around the world will begin spending significant amounts of time
developing them together, my considered view is that we are approaching
a kind of intellectual revolution:

•
The time spent in library, reference, and literature research
will be shortened by orders of magnitude, as increasingly detailed
indexes and various kinds of maps of the literature are made
available, as brilliant new search methods become available for
the entire contents of enormous libraries, and as literature
reviews (and similar resources) at all levels of specialization
are constantly updated.

•
Indeed, due to these coming sea changes in the way the results
of research are accessed, we might well see new and more efficient
methods of presenting novel research to the world than the traditional
peer-reviewed research paper. (I suggest nothing in particular
here, but as a general point it seems not unlikely.)

•
In many fields, especially in the humanities and social sciences,
what today appears to be "cutting edge" thinking will
be placed into an easily-accessible historical context. It will
appear as so much scholarship properly does appear: old ideas
warmed-over. I think the embarrassing ease of access to historical
precursors and related work will lead scholars in these fields
to focus on hard study, consolidation, systematization, and maybe
even teaching. Actually, I don't think that. That would be too
optimistic.

•
There will be—as is already becoming the case—a newly
global research community that has a presence coextensive with
the Internet itself. This, even more than the advent of the Internet
itself, has the potential to bring scholars from developing nations
around the globe into the world of research as nothing ever has
before. A well-educated, well-plugged-in intelligentsia from
every uncensored place on the map could have many remarkable
effects.

•
Perhaps more important than any of the above, the ease with which
information is accessed by teachers and students will require
a complete and long overdue rethinking of the methods of education.
What happens to education in a world in which not only *some
questionable* information is available pretty quickly (as is
now the case via Google and Wikipedia), but in which the most "officially" reliable
information is available practically instantly to everyone? What
would teachers do with their students if class were
held every day in the middle of the largest library in the world?

Those
are my expectations, and to have such expectations is of course
to be very optimistic.

I
should add that it seems the management of these information
resources will have tremendous power, due to the tremendous value
of their resources. So I hope that these managing bodies or persons
will use their power according to the love of free speech, Western
democratic republican principles of governance, and the rule
of law.

BARRY
SMITH
Philosopher, School of Advanced Study, University of London; Coeditor, Knowing
Our Own Minds

Attempts
to Dictate Our Tastes, Our Preferences, Our Culture, Our Media,
Our Political Policies, Or Moral Choices Are Bound In the End
to Fail

At
first, my suggestion may sound rather pessimistic, but what I
am optimistic about is that ultimately monopolies fail. By which
I mean, attempts to dominate our tastes, our preferences, our
culture, our media, our political policies, or moral choices.
Restless creatures that we are, we seek out variety and difference,
opportunities to extend the scope of our thinking and to exercise
discrimination and taste. This may make us hard to satisfy, but,
ultimately, it is this lack of satisfaction that leads to progress
and spells the end of hegemonies in ideology, religion, or science.

John
Stuart Mill wondered whether each of us would rather be the pig
satisfied or Socrates dissatisfied, and at times it may seem as
though a lot of people have chosen the former. But that is only
in the short term. Long term, we have no choice but to be dissatisfied
when things are constant and unchanging. The satiety of our appetites,
the endless repetition of the same thoughts and feelings, will,
eventually, in all but pathological cases, lead us to move on in
mind and seek fresh inputs. To begin with, people may readily sacrifice
their freedom for comfort, but increasingly the absence of change,
the monotony of surroundings and routines will lead to acute discomfort
and the search for something new. That is why I am optimistic that
people who are fed a constant diet of the same ideas, the same
foods, the same TV programmes, the same religious or political
dogmas will eventually come to consider other possibilities, will
switch off, change allegiance, and think differently for themselves.
It may take time; after all, some people’s threshold for
boredom is higher than others. But change and a moving on will
be inevitable. The lesson is already being learned in the corporate
world where monopolies try to cope with this by diversifying their
range of services. Their chance of survival will depend on how
cynically or sincerely they respond to this restless aspect of
the human mind. We are used to hearing how bad the diet of television
or Hollywood movies is, and how people have come to expect less
and less. But I think the opposite is true. People are increasingly
switching off and staying away from the familiar and undemanding
shows and films that lazy television executives and film producers
offer. Instead, space has opened up for intelligent and entertaining
programmes and for independent film-making. It is here, at the
creative end of the culture, that big popular success is to be
found. In similar vein, the increasingly global market has led
to a firmer appreciation of the interestingly local ones. And I
am optimistic that people, through boredom and the need for something
new, will seek out better, not worse experiences.

Human
cognition depends on change and movement in order to function.
Evolution has built us this way. Try staring at a blank wall for
several seconds without blinking and you will find the image eventually
bleaching until you can see nothing. The eye’s visual workings
respond to movement and change. So too do the other parts of our
cognitive systems. Feed them the same inputs successively and they
cease to produce very much worth having as output. Like the shark
in water, we need to keep moving or, cognitively, we die.

Science,
too, represents the greatest advert for our unquiet natures. For
as soon as a theory or school becomes the established orthodoxy,
creative minds begin to explore the possibility that we must begin
from completely different starting assumptions, and seek novel
interpretations of the data. Without this constant movement to
resist acceptance and stasis we would not have the advances or
excitements that fundamental science can provide. That said, we
must not overlook the role that luck plays in great discoveries
either. But even with a lucky finding we must be capable or recognising
and seizing on it if we are to develop insight for large-scale
revisions to our thinking. The possibility to revise, rework, and
reconsider depends on this sometimes uncomfortable fact about our
natures and our need to search for something fresh.

So far,
I have been stressing the positive aspect of the restless mind
but there is a paradox in our nature and our restless search for
change. For unless we countenance change for change’s sake,
or the relativist doctrine that anything goes (—and I don’t)
how do we preserve the very best of our thinking, select better
quality experiences, and maintain our purposes, directions and
values? How do we avoid losing sight of older wisdom while
rushing towards something new? It is here, perhaps, that our need
for variation and discrimination serves us best. For the quick
and gimmicky, the superficially appealing but weakest objects of
our thinking or targets of desire will also be the least substantial
and have an essential blandness that can tire us quickly. Besides,
the more experience we have, the larger the background against
which to compare and judge the worth or quality of what is newly
encountered, and to decide if it will be ultimately rewarding.
Certainly, people can be fickle or stubborn, but they are seldom
fickle or stubborn for long. They will seek out better, according
to what they are presently capable of responding to, and they will
be dissatisfied by something not worthy of the attention they are
capable of. For this reason attempts to dictate their tastes, cultural
goods, ideologies or ideas are bound in the end to fail, and about
that, and despite of many dark forces around us, I am optimistic.

Research
in Biology and Medicine Will Provide the First Effective Treatments
for Many Diseases

I
am optimistic that during this new century
research in biology and medicine will provide
the first effective treatments for many diseases,
although we cannot predict when they will
become available and in some cases it may
take several decades.

A
greater number of new treatments may well be developed than
was introduced during the twentieth century. I make this judgment
not only on the basis of a simple extrapolation from developments
in the past, but also on a consideration of the new understanding
that is being established at present and of the revolutionary
techniques that are emerging. Consider as examples the potential
value of the genome mapping projects, stem cells and the techniques
to assess many thousand small molecules for their ability to
have desired effects upon human cells in laboratory test systems.
All of this is underpinned by rapidly advancing molecular biology
providing essential understanding of the mechanisms that regulate
cell function.

Entirely
new opportunities are being provided by the mapping of the genomes
of people, other mammals and a variety of infectious agents that
cause human diseases such as malaria. Although we now know the
entire genetic sequence of a small number of people and have
new estimates of the number of genes in the human genome, we
have a great deal to learn about the role of specific gene products
and the mechanisms that ensure appropriate functioning of the
genes. Those actively involved in this aspect of research believe
that this stage in the development of human genetics will be
far more demanding and take far longer than the mere mechanical
reading of the sequence. However, it will in the end be very
rewarding.

It
has been appreciated for sometime that some human diseases result
directly from differences in DNA sequence, but despite considerable
research efforts only a small number of causative mutations have
been identified. Modern, rapid sequencing techniques will greatly
facilitate these analyses in the future. However, it is likely
that in a far greater number of cases sequence differences make
people comparatively vulnerable to disease, but are not directly
causative of that disease. These associations will only be revealed
by large-scale studies in which the genomes of hundreds, perhaps
thousands, of people are determined while also monitoring the
incidence of diseases in that population. This may make it possible
to provide accurate warnings to people that they are vulnerable
to specific diseases, while also offering advice on life style
and medication to reduce that risk.

In
time information of this kind may also greatly increase the accuracy
of selection of appropriate medication for particular patients.
At present an adverse response to medicines is a major cause
of death or the need for hospital treatment, even if the medicine
is appropriately prescribed and taken. This is because of differences
between people in the response to drugs. It is probably fanciful
to think of tailoring medications for each person, because this
implies a full knowledge for every person of their likely response
to and metabolism of every compound that might be considered
as a medicine. However, it does seem likely that understanding
of these mechanisms will lead to improved design and selection
of new compounds.

A
great deal has been made of the potential use of stem cells or
their derivatives to replace those lost in degenerative diseases
that reflect the death or malfunctioning of specific cell populations.
Diseases that are considered suitable for treatment in this way
include Parkinson’s disease and other neurodegenerative
diseases, juvenile diabetes, spinal cord injury, liver damage
resulting from hepatitis or solvent abuse. In their haste to
consider this use of stem cells, the potential benefit of using
such cells for drug discovery and toxicology studies is overlooked.
Drug assessment will be markedly more accurate as cells become
available that are representative of the critical tissues of
a variety of different people.

In
some cases, the cells will be genetically identical to those
of patients with an overt inherited condition. There are a number
of potential sources of such cells, but at present the most likely
seem to be embryo stem cells because they are known to have two
key characteristics. They have the ability to form all of the
different tissues of an adult and they are able to multiply almost
indefinitely in the laboratory. In practice this means that researchers
will have the opportunity to study genetically identical cell
populations again and again over a period of years and to examine
their response to potential drugs.

This
is not known to be the case for any cells taken from adults.
The gene sequence known to be associated with a specific disease
may be introduced into existing cell lines to create a population
of cells that would be expected to exhibit the characteristics
of the disease. Alternatively, it may be possible to use somatic
cell nuclear transfer from a patient with an inherited disease
to obtain embryo stem cell lines having that characteristic even
if the causative mutation is not known.

In
some cases similar research may be provide an understanding of
the molecular mechanisms that regulate the function of stem cells
in a tissue. In time, this may make it possible to stimulate
the replacement of damaged or lost cells from endogenous stem
cell populations in the patient. There would be many practical
advantages in being able to use this drug-based approach to cell
therapy. The alternative will be to produce cells of the required
type from embryo stem cells, in sufficient number that they can
replace the lost cells. When they have reached the appropriate
stage of their maturation these must then be inserted into the
damaged tissues in such a way that they are able to integrate
fully into that tissue and restore normal function. While it
is likely that each approach to cell therapy will be used for
some diseases, there are clearly many potential benefits to a
drug based therapy.

I
am optimistic that research has the potential to provide these
new opportunities, and many more not described. However, I am
concerned that society tends to be frightened by innovations
while taking for granted the treatments that are available. We
would make the most rapid progress if we recognized that it was
earlier research that led to the present treatments
and if we were excited by the challenges and opportunities
that will arise from new research.